Prostacyclin derivatives are useful pharmaceutical compounds possessing activities such as platelet aggregation inhibition, gastric secretion reduction, lesion inhibition, and bronchodilation.
Treprostinil, the active ingredient in Remodulin®, was first described in U.S. Pat. No. 4,306,075. Treprostinil, and other prostacyclin derivatives have been prepared as described in Moriarty, et al in J. Org. Chem. 2004, 69, 1890-1902, Drug of the Future, 2001, 26(4), 364-374, U.S. Pat. Nos. 6,441,245, 6,528,688, 6,700,025, 6,809,223, 6,756,117 and U.S. patent application Ser. No. 12/334,731 filed on Dec. 15, 2008 to Batra et al.
U.S. Pat. No. 5,153,222 describes use of treprostinil for treatment of pulmonary hypertension. Treprostinil is approved for the intravenous as well as subcutaneous route, the latter avoiding septic events associated with continuous intravenous catheters. U.S. Pat. Nos. 6,521,212 and 6,756,033 describe administration of treprostinil by inhalation for treatment of pulmonary hypertension, peripheral vascular disease and other diseases and conditions. U.S. Pat. No. 6,803,386 discloses administration of treprostinil for treating cancer such as lung, liver, brain, pancreatic, kidney, prostate, breast, colon and head-neck cancer. U.S. patent application publication No. 2005/0165111 discloses treprostinil treatment of ischemic lesions. U.S. Pat. No. 7,199,157 discloses that treprostinil treatment improves kidney functions. U.S. patent application publication No. 2005/0282903 discloses treprostinil treatment of neuropathic foot ulcers. U.S. Patent application publication No. 2008/0280986 discloses treprostinil treatment of pulmonary fibrosis. U.S. Pat. No. 6,054,486 discloses treatment of peripheral vascular disease with treprostinil. U.S. Patent application publication No. 2009/0036465 discloses combination therapies comprising treprostinil. U.S. Patent application publication No. 2008/0200449 discloses delivery of treprostinil using a metered dose inhaler. U.S. Patent application publication No. 2008/0280986 discloses treatment of interstitial lung disease with treprostinil and treatment of asthma with treprostinil. U.S. Pat. Nos. 7,417,070 and 7,384,978 as well as U.S. publications Nos. 2007/0078095, 2005/0282901 and 2008/0249167, describe oral formulations of treprostinil and other prostacyclin analogs.
The teachings of the aforementioned references are incorporated by reference to show how to practice the embodiments of the present invention.
In sum, treprostinil is of great importance from a medicinal point of view. Therefore, a need exists for a stable form of treprostinil which presents advantage in storage, shipment, handling, and formulation, for example.